The Endothelial Glycocalyx in Pig-to-Baboon Cardiac Xenotransplantation—First Insights

Author:

Bender Martin1ORCID,Abicht Jan-Michael1,Reichart Bruno2,Leuschen Maria2,Wall Felicia2,Radan Julia2,Neumann Elisabeth2,Mokelke Maren2,Buttgereit Ines1,Michel Sebastian34,Ellgass Reinhard3,Gieseke Katja1,Steen Stig5,Paskevicius Audrius5,Denner Joachim6ORCID,Godehardt Antonia W.7ORCID,Tönjes Ralf R.7ORCID,Hagl Christian34,Ayares David8,Wolf Eckhard91011ORCID,Schmoeckel Michael3ORCID,Brenner Paolo3,Müller Martin B.1,Längin Matthias1

Affiliation:

1. Department of Anaesthesiology, University Hospital, LMU Munich, 81377 Munich, Germany

2. Transregional Collaborative Research Center 127, Walter Brendel Centre of Experimental Medicine, LMU Munich, 81377 Munich, Germany

3. Department of Cardiac Surgery, University Hospital, LMU Munich, 81377 Munich, Germany

4. Munich Heart Alliance, German Center for Cardiovascular Research (DZHK), 81377 Munich, Germany

5. Department of Cardiothoracic Surgery, Lund University and Skåne University Hospital, 221 85 Lund, Sweden

6. Institute of Virology, Free University Berlin, 14163 Berlin, Germany

7. Division of Haematology, Cell and Gene Therapy, Paul-Ehrlich-Institut, 63225 Langen, Germany

8. Revivicor, Blacksburg, VA 24060, USA

9. Institute of Molecular Animal Breeding and Biotechnology, Gene Center, and Department of Veterinary Sciences, LMU Munich, 81377 Munich, Germany

10. Center for Innovative Medical Models (CiMM), LMU Munich, 81377 Munich, Germany

11. Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU), LMU Munich, 81377 Munich, Germany

Abstract

Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface—the endothelial glycocalyx—are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.

Funder

German Research Foundation

Swiss National Science Foundation

Bavarian Research Foundation

Leducq Foundation

Publisher

MDPI AG

Reference84 articles.

1. Cardiac xenotransplantation: From concept to clinic;Reichart;Cardiovasc. Res.,2023

2. Current status of pig heart xenotransplantation;Mohiuddin;Int. J. Surg.,2015

3. Current status of cardiac xenotransplantation;Schmoeckel;Thorac. Cardiovasc. Surg.,2023

4. Consistent success in life-supporting porcine cardiac xenotransplantation;Mayr;Nature,2018

5. Pig-to-non-human primate heart transplantation: The final step toward clinical xenotransplantation?;Reichart;J. Heart Lung Transplant.,2020

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